Preoperative cognitive profile predictive of cognitive decline after subthalamic deep brain stimulation in Parkinson's disease.

Cognitive decline represents a severe non-motor symptom of Parkinson's disease (PD) that can significantly reduce the benefits of subthalamic deep brain stimulation (STN DBS). Here, we aimed to describe post-surgery cognitive decline and identify pre-surgery cognitive profile associated with faster decline in STN DBS-treated PD patients. A retrospective observational study of 126 PD patients treated by STN DBS combined with oral dopaminergic therapy followed for 3.54 years on average (SD = 2.32) with repeated assessments of cognition was conducted. Pre-surgery cognitive profile was obtained via a comprehensive neuropsychological examination and data analysed using exploratory factor analysis and Bayesian generalized linear mixed models. On the whole, we observed a mild annual cognitive decline of 0.90 points from a total of 144 points in the Mattis Dementia Rating Scale (95% posterior probability interval [-1.19, -0.62]) with high inter-individual variability. However, true score changes did not reach previously reported reliable change cut-offs. Executive deficit was the only pre-surgery cognitive variable to reliably predict the rate of post-surgery cognitive decline. On the other hand, exploratory analysis of electrode localization did not yield any statistically clear results. Overall, our data and models imply mild gradual average annual post-surgery cognitive decline with high inter-individual variability in STN DBS-treated PD patients. Nonetheless, patients with worse long-term cognitive prognosis can be reliably identified via pre-surgery examination of executive functions. To further increase the utility of our results, we demonstrate how our models can help with disentangling true score changes from measurement error in future studies of post-surgery cognitive changes.

Porcine model of a complicated skin and soft tissue infection caused by Pseudomonas aeruginosa.

Pseudomonas aeruginosa poses a significant threat to both immunocompetent and immunocompromised individuals, often resulting in life-threatening infections. With increasing antimicrobial resistance, novel therapeutic strategies are urgently needed. Although animal models are crucial for preclinical studies, limited data are available for porcine models, more specifically for P. aeruginosa complicated skin and soft tissue infections (cSSTIs). This study presents a novel porcine model inducing and sustaining cSSTI for 14 days. Six pigs (120 wounds) were used for the development of infections, and within this group, two pigs (40 wounds) were used to evaluate the progression of the cSSTI infection. The model demonstrated bacterial loads of more than 107 CFU/gram of tissue or higher. The cSSTI fully developed within three days and remained well above these levels until day 14 post-infection. Due to the immunocompetence of this model, all the immunological processes associated with the response to the presence of infection and the wound healing process are preserved.

Structural and microstructural predictors of cognitive decline in deep brain stimulation of subthalamic nucleus in Parkinson's disease.

BACKGROUND AND OBJECTIVES: The intricate relationship between deep brain stimulation (DBS) in Parkinson's disease (PD) and cognitive impairment has lately garnered substantial attention. The presented study evaluated pre-DBS structural and microstructural cerebral patterns as possible predictors of future cognitive decline in PD DBS patients. METHODS: Pre-DBS MRI data in 72 PD patients were combined with neuropsychological examinations and follow-up for an average of 2.3 years after DBS implantation procedure using a screening cognitive test validated for diagnosis of mild cognitive impairment in PD in a Czech population - Dementia Rating Scale 2. RESULTS: PD patients who would exhibit post-DBS cognitive decline were found to have, already at the pre-DBS stage, significantly lower cortical thickness and lower microstructural complexity than cognitively stable PD patients. Differences in the regions directly related to cognition as bilateral parietal, insular and cingulate cortices, but also occipital and sensorimotor cortex were detected. Furthermore, hippocampi, putamina, cerebellum and upper brainstem were implicated as well, all despite the absence of pre-DBS differences in cognitive performance and in the position of DBS leads or stimulation parameters between the two groups. CONCLUSIONS: Our findings indicate that the cognitive decline in the presented PD cohort was not attributable primarily to DBS of the subthalamic nucleus but was associated with a clinically silent structural and microstructural predisposition to future cognitive deterioration present already before the DBS system implantation.

Mixed anxiety-depressive disorder in Parkinson's disease associated with worse resting state functional response to deep brain stimulation of subthalamic nucleus.

Background: Parkinson's disease (PD), even though generally perceived as a dominantly motor disorder, is associated with a wide range of non-motor symptoms, including mixed anxiety-depressive disorder (MADD). Objectives: The aim of the presented study was to determine whether deep brain stimulation (DBS) of the subthalamic nucleus (STN) brings the functional characteristics of non-motor networks closer to the condition detected in healthy population and whether pre-DBS presence of MADD in PD patients was associated with different reaction to this therapeutic modality. Methods: Resting-state fMRI signature elicited by STN DBS activation and deactivation in 81 PD patients was compared against healthy controls, with the focus on measures of efficiency of information processing and localised subnetwork differences. Results: While all the MRI metrics showed statistically significant differences between PD patients in DBS OFF condition and healthy controls, none were detected in such a comparison against DBS ON condition. Furthermore, in the post-DBS evaluation, PD patients with MADD in the pre-DBS stage showed no differences in depression scales compared to pre-DBS psychiatrically intact PD patients, but still exhibited lower DBS-related connectivity in a subnetwork encompassing anterior and posterior cingulate, dorsolateral prefrontal and medial temporal cortices. Conclusions: STN DBS improved all the metrics of interest towards the healthy state, normalising the resting-state MRI signature of PD. Furthermore, pre-DBS presence of MADD, even though clinically silent at post-DBS MRI acquisition, was associated with lower DBS effect in areas highly relevant for depression. This finding points to a possibly latent nature of post-DBS MADD, calling for caution in further follow-up of these patients.

Phytocannabinoids and gingival inflammation: Preclinical findings and a placebo-controlled double-blind randomized clinical trial with cannabidiol.

OBJECTIVE: The aim of this study was to: (1) evaluate the anti-inflammatory effects of cannabidiol (CBD) on primary cultures of human gingival fibroblasts (HGFs) and (2) to clinically monitor the effect of CBD in subjects with periodontitis. BACKGROUND: The use of phytocannabinoids is a new approach in the treatment of widely prevalent periodontal disease. MATERIALS AND METHODS: Cannabinoid receptors were analyzed by western blot and interleukin production detected using enzyme immunoassay. Activation of the Nrf2 pathway was studied via monitoring the mRNA level of heme oxygenase-1. Antimicrobial effects were determined by standard microdilution and 16S rRNA screening. In the clinical part, a placebo-control double-blind randomized study was conducted (56 days) in three groups (n = 90) using dental gel without CBD (group A) and with 1% (w/w) CBD (group B) and corresponding toothpaste (group A - no CBD, group B - with CBD) for home use to maintain oral health. Group C used dental gel containing 1% chlorhexidine digluconate (active comparator) and toothpaste without CBD. RESULTS: Human gingival fibroblasts were confirmed to express the cannabinoid receptor CB2. Lipopolysaccharide-induced cells exhibited increased production of pro-inflammatory IL-6 and IL-8, with deceasing levels upon exposure to CBD. CBD also exhibited antimicrobial activities against Porphyromonas gingivalis, with an MIC of 1.5 µg/mL. Activation of the Nrf2 pathway was also demonstrated. In the clinical part, statistically significant improvement was found for the gingival, gingival bleeding, and modified gingival indices between placebo group A and CBD group B after 56 days. CONCLUSIONS: Cannabidiol reduced inflammation and the growth of selected periodontal pathogenic bacteria. The clinical trial demonstrated a statistically significant improvement after CBD application. No adverse effects of CBD were reported by patients or observed upon clinical examination during the study. The results are a promising basis for a more comprehensive investigation of the application of non-psychotropic cannabinoids in dentistry.

Identification of staphyloxanthin and derivates in yellow-pigmented Staphylococcus capitis subsp. capitis.

Introduction: Staphylococcus capitis naturally colonizes the human skin but as an opportunistic pathogen, it can also cause biofilm-associated infections and bloodstream infections in newborns. Previously, we found that two strains from the subspecies S. capitis subsp. capitis produce yellow carotenoids despite the initial species description, reporting this subspecies as non-pigmented. In Staphylococcus aureus, the golden pigment staphyloxanthin is an important virulence factor, protecting cells against reactive oxygen species and modulating membrane fluidity. Methods: In this study, we used two pigmented (DSM 111179 and DSM 113836) and two non-pigmented S. capitis subsp. capitis strains (DSM 20326T and DSM 31028) to identify the pigment, determine conditions under which pigment-production occurs and investigate whether pigmented strains show increased resistance to ROS and temperature stress. Results: We found that the non-pigmented strains remained colorless regardless of the type of medium, whereas intensity of pigmentation in the two pigmented strains increased under low nutrient conditions and with longer incubation times. We were able to detect and identify staphyloxanthin and its derivates in the two pigmented strains but found that methanol cell extracts from all four strains showed ROS scavenging activity regardless of staphyloxanthin production. Increased survival to cold temperatures (-20°C) was detected in the two pigmented strains only after long-term storage compared to the non-pigmented strains. Conclusion: The identification of staphyloxanthin in S. capitis is of clinical relevance and could be used, in the same way as in S. aureus, as a possible target for anti-virulence drug design.

European candidaemia is characterised by notable differential epidemiology and susceptibility pattern: Results from the ECMM Candida III study.

The objectives of this study were to assess Candida spp. distribution and antifungal resistance of candidaemia across Europe. Isolates were collected as part of the third ECMM Candida European multicentre observational study, conducted from 01 to 07-07-2018 to 31-03-2022. Each centre (maximum number/country determined by population size) included ∼10 consecutive cases. Isolates were referred to central laboratories and identified by morphology and MALDI-TOF, supplemented by ITS-sequencing when needed. EUCAST MICs were determined for five antifungals. fks sequencing was performed for echinocandin resistant isolates. The 399 isolates from 41 centres in 17 countries included C. albicans (47.1%), C. glabrata (22.3%), C. parapsilosis (15.0%), C. tropicalis (6.3%), C. dubliniensis and C. krusei (2.3% each) and other species (4.8%). Austria had the highest C. albicans proportion (77%), Czech Republic, France and UK the highest C. glabrata proportions (25-33%) while Italy and Turkey had the highest C. parapsilosis proportions (24-26%). All isolates were amphotericin B susceptible. Fluconazole resistance was found in 4% C. tropicalis, 12% C. glabrata (from six countries across Europe), 17% C. parapsilosis (from Greece, Italy, and Turkey) and 20% other Candida spp. Four isolates were anidulafungin and micafungin resistant/non-wild-type and five resistant to micafungin only. Three/3 and 2/5 of these were sequenced and harboured fks-alterations including a novel L657W in C. parapsilosis. The epidemiology varied among centres and countries. Acquired echinocandin resistance was rare but included differential susceptibility to anidulafungin and micafungin, and resistant C. parapsilosis. Fluconazole and voriconazole cross-resistance was common in C. glabrata and C. parapsilosis but with different geographical prevalence.

Gene expression and metabolic activity of Streptococcus mutans during exposure to dietary carbohydrates glucose, sucrose, lactose, and xylitol.

Recent RNA sequencing studies have given us a deeper insight into the cariogenic impact of carbohydrate sources in the bacterium Streptococcus mutans, the principal microbial agent in dental caries etiopathogenesis. The process of dental caries development is facilitated by the ability of this bacterium to ferment some carbohydrates into organic acids contributing to a pH decrease in the oral cavity and the demineralization of the hard tissues of the tooth. Furthermore, in dental caries progression, biofilm formation, which starts and ends with free planktonic cells, plays an important role and has several unique properties called virulence factors. The most cariogenic carbohydrate is sucrose, an easily metabolizable source of energy that induces the acidification and synthesis of glucans, forming typical bacterial cell clumps. We used multifaceted methodological approaches to compare the transcriptomic and metabolomic profiles of S. mutans growing in planktonic culture on preferred and nonpreferred carbohydrates and in fasting conditions. Streptococcus mutans in a planktonic culture with lactose produced the same pH drop as glucose and sucrose. By contrast, xylitol and lactose showed high effectiveness in regulating intracellular polysaccharide metabolism, cell wall structure, and overall virulence involved in the initial phase of biofilm formation and structure but with an opposite pattern compared with sucrose and glucose. Our results confirmed the recent findings that xylitol and lactose play a vital role in biofilm structure. However, they do not reduce its formation, which is related to the creation of a cariogenic environment.

Rapid Identification of Pathogens Causing Bloodstream Infections by Raman Spectroscopy and Raman Tweezers.

The search for the "Holy Grail" in clinical diagnostic microbiology-a reliable, accurate, low-cost, real-time, easy-to-use method-has brought up several methods with the potential to meet these criteria. One is Raman spectroscopy, an optical, nondestructive method based on the inelastic scattering of monochromatic light. The current study focuses on the possible use of Raman spectroscopy for identifying microbes causing severe, often life-threatening bloodstream infections. We included 305 microbial strains of 28 species acting as causative agents of bloodstream infections. Raman spectroscopy identified the strains from grown colonies, with 2.8% and 7% incorrectly identified strains using the support vector machine algorithm based on centered and uncentred principal-component analyses, respectively. We combined Raman spectroscopy with optical tweezers to speed up the process and captured and analyzed microbes directly from spiked human serum. The pilot study suggests that it is possible to capture individual microbial cells from human serum and characterize them by Raman spectroscopy with notable differences among different species. IMPORTANCE Bloodstream infections are among the most common causes of hospitalizations and are often life-threatening. To establish an effective therapy for a patient, the timely identification of the causative agent and characterization of its antimicrobial susceptibility and resistance profiles are essential. Therefore, our multidisciplinary team of microbiologists and physicists presents a method that reliably, rapidly, and inexpensively identifies pathogens causing bloodstream infections-Raman spectroscopy. We believe that it might become a valuable diagnostic tool in the future. Combined with optical trapping, it offers a new approach where the microorganisms are individually trapped in a noncontact way by optical tweezers and investigated by Raman spectroscopy directly in a liquid sample. Together with the automatic processing of measured Raman spectra and comparison with a database of microorganisms, it makes the whole identification process almost real time.

Improving fMRI in Parkinson's disease by accounting for brain region-specific activity patterns.

In functional magnetic imaging (fMRI) in Parkinson's disease (PD), a paradigm consisting of blocks of finger tapping and rest along with a corresponding general linear model (GLM) is often used to assess motor activity. However, this method has three limitations: (i) Due to the strong magnetic field and the confined environment of the cylindrical bore, it is troublesome to accurately monitor motor output and, therefore, variability in the performed movement is typically ignored. (ii) Given the loss of dopaminergic neurons and ongoing compensatory brain mechanisms, motor control is abnormal in PD. Therefore, modeling of patients' tapping with a constant amplitude (using a boxcar function) and the expected Parkinsonian motor output are prone to mismatch. (iii) The motor loop involves structures with distinct hemodynamic responses, for which only one type of modeling (e.g., modeling the whole block of finger tapping) may not suffice to capture these structure's temporal activation. The first two limitations call for considering results from online recordings of the real motor output that may lead to significant sensitivity improvements. This was shown in previous work using a non-magnetic glove to capture details of the patients' finger movements in a so-called kinematic approach. For the third limitation, modeling motion initiation instead of the whole tapping block has been suggested to account for different temporal activation signatures of the motor loop's structures. In the present study we propose improvements to the GLM as a tool to study motor disorders. For this, we test the robustness of the kinematic approach in an expanded cohort (n = 31), apply more conservative statistics than in previous work, and evaluate the benefits of an event-related model function. Our findings suggest that the integration of the kinematic approach offers a general improvement in detecting activations in subcortical structures, such as the basal ganglia. Additionally, modeling motion initiation using an event-related design yielded superior performance in capturing medication-related effects in the putamen. Our results may guide adaptations in analysis strategies for functional motor studies related to PD and also in more general applications.

SERS-Tags: Selective Immobilization and Detection of Bacteria by Strain-Specific Antibodies and Surface-Enhanced Raman Scattering.

Efficient separation and sensitive identification of pathogenic bacterial strains is essential for a prosperous modern society, with direct applications in medical diagnostics, drug discovery, biodefense, and food safety. We developed a fast and reliable method for antibody-based selective immobilization of bacteria from suspension onto a gold-plated glass surface, followed by detection using strain-specific antibodies linked to gold nanoparticles decorated with a reporter molecule. The reporter molecules are subsequently detected by surface-enhanced Raman spectroscopy (SERS). Such a multi-functionalized nanoparticle is called a SERS-tag. The presented procedure uses widely accessible and cheap materials for manufacturing and functionalization of the nanoparticles and the immobilization surfaces. Here, we exemplify the use of the produced SERS-tags for sensitive single-cell detection of opportunistic pathogen Escherichia coli, and we demonstrate the selectivity of our method using two other bacterial strains, Staphylococcus aureus and Serratia marcescens, as negative controls. We believe that the described approach has a potential to inspire the development of novel medical diagnostic tools for rapid identification of bacterial pathogens.

Rapid identification of pathogens in blood serum via Raman tweezers in combination with advanced processing methods.

Pathogenic microbes contribute to several major global diseases that kill millions of people every year. Bloodstream infections caused by these microbes are associated with high morbidity and mortality rates, which are among the most common causes of hospitalizations. The search for the "Holy Grail" in clinical diagnostic microbiology, a reliable, accurate, low cost, real-time, and easy-to-use diagnostic method, is one of the essential issues in clinical practice. These very critical conditions can be met by Raman tweezers in combination with advanced analysis methods. Here, we present a proof-of-concept study based on Raman tweezers combined with spectral mixture analysis that allows for the identification of microbial strains directly from human blood serum without user intervention, thus eliminating the influence of a data analyst.

Effect of fixed orthodontic appliances on gingival status and oral microbiota: a pilot study.

BACKGROUND: This pilot study aimed to investigate how fixed orthodontic appliances simultaneously applied on the upper and lower arches affect the oral environment in the medium term. METHODS: The oral status of 30 orthodontic patients was evaluated using the number of decay-missing-filled teeth (DMFT), plaque (PI), and gingival indices (GI) before bonding of fixed orthodontic appliances (T0) and during the therapy (T1). Besides, the gingival crevicular fluid (GCF) and a dental plaque were collected. Samples were analyzed for selected Candida sp. and for 10 selected oral bacteria using mass spectroscopy and multiplex polymerase chain reaction, respectively. RESULTS: In 60% of patients, deterioration of the oral status (demonstrated by the increase in PI) was recorded (p < 0.05). Moreover, the changes in PI correlated with those of GI (p < 0.001). At the T1 time point, the mean representation of Actinomyces sp. in the total prokaryotic DNA in GCF and dental plaque of individual patients increased compared to T0 (p < 0.05). The probability of finding any of the 7 selected periodontal bacteria combined with Candida sp. was 10 times higher in patients in whom PI deteriorated between T0 and T1 (p < 0.01). CONCLUSIONS: Changes in the oral microbial diversity and an increase in PI were observed in the medium term after bonding of orthodontic appliance. Our study highlights the importance of a complex approach in this type of research as the association between clinical characteristics and combined microbial parameters is higher than when evaluated separately.

Polygenic signals of sex differences in selection in humans from the UK Biobank.

Sex differences in the fitness effects of genetic variants can influence the rate of adaptation and the maintenance of genetic variation. For example, "sexually antagonistic" (SA) variants, which are beneficial for one sex and harmful for the other, can both constrain adaptation and increase genetic variability for fitness components such as survival, fertility, and disease susceptibility. However, detecting variants with sex-differential fitness effects is difficult, requiring genome sequences and fitness measurements from large numbers of individuals. Here, we develop new theory for studying sex-differential selection across a complete life cycle and test our models with genotypic and reproductive success data from approximately 250,000 UK Biobank individuals. We uncover polygenic signals of sex-differential selection affecting survival, reproductive success, and overall fitness, with signals of sex-differential reproductive selection reflecting a combination of SA polymorphisms and sexually concordant polymorphisms in which the strength of selection differs between the sexes. Moreover, these signals hold up to rigorous controls that minimise the contributions of potential confounders, including sequence mapping errors, population structure, and ascertainment bias. Functional analyses reveal that sex-differentiated sites are enriched in phenotype-altering genomic regions, including coding regions and loci affecting a range of quantitative traits. Population genetic analyses show that sex-differentiated sites exhibit evolutionary histories dominated by genetic drift and/or transient balancing selection, but not long-term balancing selection, which is consistent with theoretical predictions of effectively weak SA balancing selection in historically small populations. Overall, our results are consistent with polygenic sex-differential-including SA-selection in humans. Evidence for sex-differential selection is particularly strong for variants affecting reproductive success, in which the potential contributions of nonrandom sampling to signals of sex differentiation can be excluded.

Capillary electrophoretic methods for classification of methicillin-resistant Staphylococcus aureus (MRSA) clones.

This study describes differentiation of methicillin-resistant Staphylococcus aureus (MRSA) isolates belonging to different genotype groups by the combination of electrophoretic techniques, transient isotachophoresis and micellar electrokinetic chromatography. MRSA isolates were separated in fused silica capillary with roughened inner surface prepared by etching with supercritical water. Separation temperature together with the rinsing procedure of the capillary turned out to be the key factors of successful analysis. The individual genotype groups were baseline-resolved in 40 min. Partial separation of the individual isolates within the groups was also observed. Relative standard deviations of the migration times of the isolate zones ranged from 0.32 to 0.79%. In addition, capability of the developed CE method to concentrate and separate MRSA isolates in clinical samples was proved by the analysis of blood sample.

Restoration of functional network state towards more physiological condition as the correlate of clinical effects of pallidal deep brain stimulation in dystonia.

BACKGROUND: Deep brain stimulation of the internal globus pallidus (GPi DBS) is an invasive therapeutic modality intended to retune abnormal central nervous system patterns and relieve the patient of dystonic or other motor symptoms. OBJECTIVES: The aim of the presented research was to determine the neuroanatomical signature of GPi DBS modulation and its association with the clinical outcome. METHODS: This open-label fixed-order study with cross-sectional validation against healthy controls analysed the resting-state functional MRI activity changes induced by GPi DBS in 18 dystonia patients of heterogeneous aetiology, focusing on both global (full brain) and local connectivity (local signal homogeneity). RESULTS: Compared to the switched-off state, the activation of GPi DBS led to the restoration of global subcortical connectivity patterns (in both putamina, diencephalon and brainstem) towards those of healthy controls, with positive direct correlation over large-scale cortico-basal ganglia-thalamo-cortical and cerebellar networks with the clinical improvement. Nonetheless, on average, GPi DBS also seemed to bring local connectivity both in the cortical and subcortical regions farther away from the state detected in healthy controls. Interestingly, its correlation with clinical outcome showed that in better DBS responders, local connectivity defied this effect and approached healthy controls. CONCLUSIONS: All in all, the extent of restoration of both these main metrics of interest towards the levels found in healthy controls clearly correlated with the clinical improvement, indicating that the restoration of network state towards more physiological condition may be a precondition for successful GPi DBS outcome in dystonia.

How much does the unguarded X contribute to sex differences in life span?

Females and males often have markedly different mortality rates and life spans, but it is unclear why these forms of sexual dimorphism evolve. The unguarded X hypothesis contends that dimorphic life spans arise from sex differences in X or Z chromosome copy number (i.e., one copy in the "heterogametic" sex; two copies in the "homogametic" sex), which leads to a disproportionate expression of deleterious mutations by the heterogametic sex (e.g., mammalian males; avian females). Although data on adult sex ratios and sex-specific longevity are consistent with predictions of the unguarded X hypothesis, direct experimental evidence remains scant, and alternative explanations are difficult to rule out. Using a simple population genetic model, we show that the unguarded X effect on sex differential mortality is a function of several reasonably well-studied evolutionary parameters, including the proportion of the genome that is sex linked, the genomic deleterious mutation rate, the mean dominance of deleterious mutations, the relative rates of mutation and strengths of selection in each sex, and the average effect of mutations on survival and longevity relative to their effects on fitness. We review published estimates of these parameters, parameterize our model with them, and show that unguarded X effects are too small to explain observed sex differences in life span across species. For example, sex differences in mean life span are known to often exceed 20% (e.g., in mammals), whereas our parameterized models predict unguarded X effects of a few percent (e.g., 1-3% in Drosophila and mammals). Indeed, these predicted unguarded X effects fall below statistical thresholds of detectability in most experiments, potentially explaining why direct tests of the hypothesis have generated little support for it. Our results suggest that evolution of sexually dimorphic life spans is predominantly attributable to other mechanisms, potentially including "toxic Y" effects and sexual dimorphism for optimal investment in survival versus reproduction.

Evolutionary genetics: Dissecting a sexually antagonistic polymorphism.

Males and females experience divergent selection on many shared traits, which can lead to 'sexual antagonism' - opposing fitness effects of genetic variants in each sex. A new study in the fly Drosophila serrata links sexually antagonistic selection on cuticular hydrocarbons to a single major-effect gene.

Candida species and selected behavioral factors co-associated with severe early childhood caries: Case-control study.

Severe Early Childhood Caries (sECC) is a multifactorial disease associated with the occurrence of specific oral microorganisms and other environmental, behavioral, and genetic factors. This study aimed to construct a multivariable model including the occurrence of Candida spp. and selected behavioral factors (length of breastfeeding, serving sweet beverages and beginning of brushing child's teeth) to determine their relationships to the occurrence of sECC. In this case-control study 164 children with sECC and 147 children without dental caries were included. MALDI-TOF MS and multiplex qPCR were used to identify Candida spp. and selected bacteria in dental plaque samples, respectively. A questionnaire on oral hygiene, diet, and children's health was filled in by the parents. The constructed multivariable logistic regression model showed an independent influence of the microbial and behavioral factors in sECC etiopathogenesis. The occurrence of C. albicans and C. dubliniensis was associated with higher odds of sECC development (odds ratio, OR: 9.62 and 16.93, respectively), together with breastfeeding of 6 months or less (OR: 2.71), exposure to sweet beverages (OR: 3.77), and starting to brush child's teeth after the 12th month of age (OR: 4.10), all statistically significant (p < 0.01). Considering the high occurrence of C. albicans and C. dubliniensis in dental plaque in children with sECC, we propose them as "keystone pathogens" and risk factors for sECC. The models showed that presence of specific species of Candida in dental plaque may be a better descriptor of sECC than the mentioned behavioral factors.

The Instrumental Activities of Daily Living in Parkinson's Disease Patients Treated by Subthalamic Deep Brain Stimulation.

Background: Everyday functioning and instrumental activities of daily living (IADL) play a vital role in preserving the quality of life in patients with Parkinson's disease (PD) after deep brain stimulation of the subthalamic nucleus (STN-DBS). Objective: The main goal of the current study was to examine IADL change in pre-and post-surgery of the STN-DBS. We also analyzed the influence of the levodopa equivalent daily dose (LEDD) and global cognitive performance (Dementia Rating Scale; DRS-2) as covariates in relation to IADL. Methods: Thirty-two non-demented PD patients were administered before and after STN-DBS neurosurgery the Penn Parkinson's Daily Activities Questionnaire (PDAQ; self-report), the DRS-2 and Beck Depression Inventory (BDI-II) to assess IADL change, global cognition, and depression. Results: We found a positive effect of STN-DBS on IADL in the post-surgery phase. Moreover, lower global cognition and lower LEDD are predictive of lower IADL in both pre-surgery and post-surgery examinations. Summary/Conclusion: STN-DBS in PD is a safe method for improvement of everyday functioning and IADL. In the post-surgery phase, we show a relation of IADL to the severity of cognitive impairment in PD and to LEDD.